Esophageal Cancer Approx. 13,000 cases/year in USA Post-esophagectomy overall 5 yr survival = 18% At presentation, 57% patients are Stage 3, with a 10% post-esophagectomy surv. At presentation, 24% patients are Stage 2, with a 35% post-esophagectomy surv. At presentation, patients who are Stage 1, have an 80% post-esophagectomy surv.

Esophageal CA -- pre-op staging TNM staging somewhat overbroad If T1, but tumor is in mucosa only: Lymph node metastases < 10% If T1, but tumor extends into submucosa: Lymph node metastases = approx. 30 Distant mets, lymph nodes, wall penetration

Esophageal CA -- find distant mets CT chest and abdomen -- mostly useful in trying to detect distant mets but, CT chest and abdomen -- only 60% accurate in detecting regional lymph node disease but, CT chest and abdomen -- underestimates tumor stage in 40% of patients Addition of PET may improve accuracy

Esophageal CA -- find distant mets Bronchoscopy in proximal and middle third esophageal CA’s eval. for posterior tracheal invasion “slight compression” still resectable “abnormal tracheal mucosa” unresectable

Esophageal CA -- eval. lymph nodes Lymph node status Thoracoscopic staging can find LNs, but poorly predicts unresectability Laparoscopic staging can change treatment in 30% of distal esophageal Cas Matted celiac nodes Carcinomatosis Small liver lesions

Esophageal CA -- eval. lymph nodes Lymph node status Laparascopic staging Laparscopic ultrasound of liver not useful

Esophageal CA -- pre-op staging Wall penetration Endoscopic ultrasound -- incorrect in determining wall depth 15-20% of the time Endoscopic ultrasound -- incorrect in determining nodal status 25 - 30% of the time Endoscopic ultrasound -- less accurate after neoadjuvant therapy

Esophageal CA -- pre-op staging Wall penetration “High grade dysplasia” = 43% occult adeno CA Tumor limited to submucosa --> 19% LN involvement 3% had more than 4 nodes Nodes limited to peri-esophageal, not spleen or peri-gastric => no need to resect these Invasion of muscularis propria --> 80% LN involvement

Esophageal CA -- chemoradiation Treatment of choice for Stage 4 (mets) Stent esophageal lesion, chemo and radiation SCC responds to radiation better than Adeno CA

Esophagectomy -- Types of operations Incision strategies: Ivor-Lewis Laparotomy, thoracotomy Transhiatal Conduit strategies: Gastric pull-up Colonic interposition Jejunal interposition

Esophagectomy -- Types of operations Anastomosis strategies: Location: Cervical Intrathoracic Anastomotic technique does not affect leak rate Radiation, vascular supply does Post-op feeding strategies: Jejunosotmy feeding tube placed at time of esophagectomy

Esophagectomy -- Types of operations Anastomosis strategies: Technique: Stapled (EEA) Ease Strictures Sutured single layer vs double layer, running vs interrupted

Esophagectomy -- Types of operations Anastomosis strategies: Tension issues Tacking sutures not often used in stapled anastomoses Gastric emptying strategies 15% pyloric obstruction rate Pyloroplasty, pyloromyotomy ? +/- Graham patch Vagotomy

Esophagectomy -- Intra-operative complications Bleeding average < 800 cc for Ivor-Lewis transhiatal esophagectomy bleeding left thoracoabdominal extension vs. left thoractomy Aortic a., bronchial a., azygous v. bleeding --> pack, then upper sternal split Tracheobronchial injury secure airway by advancing ETT, then repair primarily vs. pedicled flap buttress

Esophagectomy -- Intra-operative complications Recurrent laryngeal nerve injury especially in cervical dissections

Esophagectomy -- Operation by stage Barrett’s esophagus with High-grade dysplasia or intramucosal adeno-CA No visible tumor on endoscopic U/S but again, U/S may not be accurate in distinguishing mucosal vs. submucosal confinement Vagal sparing esophagectomy, transhiatal esophagectomy If no regional disease detected

Esophagectomy -- Operation by stage Barrett’s esophagus with High-grade dysplasia or intramucosal adeno-CA No visible tumor on endoscopic U/S but again, U/S may not be accurate in distinguishing mucosal vs. submucosal confinement Investigational: Mucosal ablation (laser, photodynamic), endoscopic mucosal resection

Esophagectomy -- Operation by Stage Tumor confined to submucosa on U/S Visible tumor on endoscopic U/S 75% have tumor past mucosa into submucosa and beyond when seen on U/S 56% have lymph node metastases (both limited to and extending past submucosa) Extended transhiatal esophagectomy Complete lower mediastinal and upper abdominal lymph node resection since only 19% had LNs if limited to submucosa not “en bloc” since only 3% had > 4 LNs

Esophagectomy -- Operation by Stage Tumor into or through muscularis propria 75% to 85% LN involvement 45% have > 4 LNs 30 - 40% have distant LNs involved (25% celiac LNs) radical en bloc esophagectomy (DeMeester) 1-5 % local recurrence rate however, most surgeons do not perform radical en bloc resections, relying on adjuvant therapy 35% local recurrence operation alone (i.e. not “en bloc”)

Esophagectomy -- Operation by Stage Radical en bloc esophagectomy (DeMeester) 1-5 % local recurrence rate Compare 35% local recurrence overall after esophagectomy Five-year survival for Stage 3 is 23 - 50% Compare overall five-year Stage 3 post-esophagectomy survival rate of 10% Cervical lymph node dissection Mid-thoracic tumors and upper third tumors have 45% cervical lymph node mets

Esophagectomy -- Operation by Stage Cervical lymph node dissection Mid-thoracic tumors and upper third tumors have 45% cervical lymph node mets No survival advantage to cervical LN resection (Nishimaki, 1999) Exception was 1 to 4 LNs (but how can you tell in advance?) Significant additonal morbidity (80%) with additional lymph node (“three-field”) dissection

Esophagectomy -- Complications Mortality 3 - 5%, Morbidity 15-18% Anastomotic leaks -- 1 - 5% Cervical leak rate 0-12%, post-op day 5-10 fever, crepitance, drainage, erythema, leukocytosis requires wide incision and drainage, not repair 1/3 develop stricture --> I&D (not repair)

Esophagectomy -- Complications Thoracic --> Gastrograffin swallow vs. CT With-hold feeding additional 5-7 days if < 1 cm contained leak Repeat esophagogram Exploration if free leak or > 1 cm contained leak (risk of erosion by mass effect) Pediatric endoscope at exploration time (?) Assess for large disruptions or necrosis of conduit

Esophagectomy -- Complications Conduit necrosis or large disruptions Resect anastomosis, debride edges End cervical diverting esophagostomy Gastric remnant returned to abdomen Drainage Reconstruction in several months

Esophagectomy -- Complications Conduit obstruction at diaphragm Two fingers width alongside conduit at diaphragm Resect head of left clavicle, first rib, manubrium in cervical anastomoses as needed Diaphragmatic bowel herniation Prevent by suturing conduit to hiatus with 3 - 4 sutures Vague lower thoracic/upper abd. cramping pains CXR; CT or contrast study if in doubt Repair with hiatal closure and anchoring sutures

Esophagectomy -- Complications Chylothorax 1 - 3% Ligate intraoperatively when identified Massive (800 cc/day) chest tube output at 5 - 7 days post-op vs. tension chylothorax if no Chest Tube Feed cream -- note change in chest tube character Stop enteral feeds; start TPN Explore promptly and ligate thoracic duct through right thoracotomy, VATS, or prior thoracotomy

Esophagectomy -- Complications Anastomotic strictures -- 5 - 42% More often if lye, leak, small EEA staplers, suture technique, irradiation Requires dilatation (80% dilatation success) Early after leak Combined with endoscopy Use 46 Fr or larger Maloney dilators, balloons when necessary Repeat until 6 months of stability use extra care if colon, small bowel conduit Chronic (> 12 mo) cervical anastomotic strictures Stricturoplasty / SCM flap (50% failure) / Lat. Dorsi flap / free radial arm flap / pectoralis myocutaneous flap (like ENT flaps)

Esophagectomy -- Complications Delayed hemorrhage (rare) Consider splenic injury Aspiration pneumonia -- 3% Videoesophagogram before re-feeding 5-7 days Dysphagia Regurgitation Delayed emptying Only 15% develop pyloric obstruction Balloon dilatation, erythromycin, metoclopramide Dumping

Esophagectomy -- Post-op diet Smaller, more frequent meals Drink liquids after meals to avoid gastric distension Avoid high carbohydrate diets Liberal anti-diarrheal use Dumping symptoms usually resolve in 6 - 12 months

Esophageal CA -- radiation 20 to 40 Gy over 2 - 4 weeks (1.75 to 3.75 Gy/fx) Squamous cell carcinoma -- more radiosensitive Preoperative radiation versus surgery alone no improved survival in long-term randomized trials Post-op radiation versus surgery alone no improved survival, but higher stricture rate improved local recurrence rates in node negative mid- to upper-third SCCs

Esophageal CA -- chemo Pre-operative chemo (Cisplatin, 5-FU) Only 19% response No change in survival No change in local recurrence rates or patterns

Esophageal CA -- chemoradiation Pre-op chemoradiation (cisplatin/5-FU) 40% (histologic) response rate (average) Similar response rates for SCC and AdenoCA Response rate dependent on time to surgery following chemoradiation What is ideal delay to surgery? In rectal CA, 6-8 week gap allows more restorative surgery than does a 2 week gap Allow healing ability to recover Allow clinical tumor shrinkage

Esophageal CA -- chemoradiation Pre-op chemoradiation (cisplatin/5-FU) Increases surgical M/M by 5-15% With high does rad’n (high dose (3.5 Gy) /fraction (TE fistula) Anastomotic leaks, strictures Toxicities myelotoxicity if Mitomycin C, etoposide, vinblastine added Average results, not controlled by delay to surgery

Esophageal CA -- chemoradiation Pre-op chemoradiation (cisplatin/5-FU) Non-significant improvements yet seen Urba(2001, AdenoCA only) : 3 year survival 16% --> 30% (P=0.15) Local recurrence 41% --> 19% Clark(2000abstract) : 2 year 35% --> 45% (P=.002) median survival difference 4 months, short F/U Walsh (1996, adenoCA only) : highly controversial: 6% --> 32% Bossett(1997, Stage 1 and 2 SCC only): no difference

Esophageal CA -- chemoradiation Pre-op chemoradiation (cisplatin/5-FU) Survival differences may be lost by 5 years Benefits not yet substantiated by long-term studies (2002 review)

Esophageal CA -- chemoradiation alone Chemoradiation instead of surgery Studies show pathologic and clinical response rates comparable to historical esophagectomy survivals in Stage 2 and 3 carcinomas EORTC trial in progress -- 30 Gy with 5 FU/Cisplatin Comparisons are not against “en bloc” resections

Esophageal CA -- chemoradiation alone Chemoradiation (CRT) instead of surgery 40-60% of CRT alone die with local recurrence/failure Compare 9% with CRT plus surgery Surgical salvage following CRT alone no difference in salvage versus CRT alone

Esophageal CA -- chemoradiation alone Chemoradiation instead of surgery Current methods to determine complete (clinical) response are inadequate to predict which patients might not require surgery in addition to chemoradiation Endoscopic U/S or MRI -- accuracy inadequate in determining local and regional tumor PET, CT -- can’t detect regional nodes well Histologic response -- not avail. without resection Future: biologic serum markers ?